This study demonstrates a remarkable microscopic dose enhancement due to GNPs and low energy photon sources. By quantifying the microscopic dose enhancement factor for a given photon source as a function of distance from GNPs, it also enables the selection of either a passive or an active tumor targeting strategy using GNPs which will maximize the radiobiological benefit from GNRT.
The preferential accumulation of gold nanoparticles within tumors and the increased photoelectric absorption due to the high atomic number of gold cooperatively account for the possibility of significant tumor dose enhancement during gold nanoparticle-aided radiation therapy (GNRT). Among the many conceivable ways to implement GNRT clinically, a brachytherapy approach using low-energy gamma-/x-ray sources (i.e. Eavg < 100 keV) appears to be highly feasible and promising, because it may easily fulfill some of the technical and clinical requirements for GNRT. Therefore, the current study investigated the dosimetric feasibility of implementing GNRT using the following sources: 125I, 50 kVp and 169Yb. Specifically, Monte Carlo (MC) calculations were performed to determine the macroscopic dose enhancement factors (MDEF), defined as the ratio of the average dose in the tumor region with and without the presence of gold nanoparticles during the irradiation of the tumor, and the photo/Auger electron spectra within a tumor loaded with gold nanoparticles. The current study suggests that a significant tumor dose enhancement (e.g. >40%) could be achievable using 125I, 50 kVp and 169Yb sources and gold nanoparticles. When calculated at 1.0 cm from the center of the source within a tumor loaded with 18 mg Au g−1, macroscopic dose enhancement was 116, 92 and 108% for 125I, 50 kVp and 169Yb, respectively. For a tumor loaded with 7 mg Au g−1, it was 68, 57 and 44% at 1 cm from the center of the source for 125I, 50 kVp and 169Yb, respectively. The estimated MDEF values for 169Yb were remarkably larger than those for 192Ir, on average by up to about 70 and 30%, for 18 mg Au and 7 mg Au cases, respectively. The current MC study also shows a remarkable change in the photoelectron fluence and spectrum (e.g. more than two orders of magnitude) and a significant production (e.g. comparable to the number of photoelectrons) of the Auger electrons within the tumor region due to the presence of gold nanoparticles during low-energy gamma-/x-ray irradiation. The radiation sources considered in this study are currently available and tumor gold concentration levels considered in this investigation are deemed achievable. Therefore, the current results strongly suggest that GNRT can be successfully implemented via brachytherapy with low energy gamma-/x-ray sources, especially with a high dose rate 169Yb source.
BACKGROUND:
Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality.
METHODS:
The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching.
RESULTS:
A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P=.002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P=.001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P=.045]).
CONCLUSIONS:
Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival.
In this large contemporary analysis, men with mPCa receiving prostate RT and ADT lived substantially longer than men treated with ADT alone. Prospective trials evaluating local therapies for mPCa are warranted.
A conventional x-ray fluorescence computed tomography (XFCT) technique requires monochromatic synchrotron x-rays to simultaneously determine the spatial distribution and concentration of various elements such as metals in a sample. However, the synchrotron-based XFCT technique appears to be unsuitable for in vivo imaging under a typical laboratory setting. In this study we demonstrated, for the first time to our knowledge, the possibility of performing XFCT imaging of a small animal-sized object containing gold nanoparticles (GNPs) at relatively low concentrations using polychromatic diagnostic energy range x-rays. Specifically, we created a phantom made of polymethyl methacrylate plastic containing two cylindrical columns filled with saline solution at 1 and 2 wt% GNPs, respectively, mimicking tumors/organs within a small animal. XFCT scanning of the phantom was then performed using microfocus 110 kVp x-ray beam and cadmium telluride (CdTe) x-ray detector under a pencil beam geometry after proper filtering of the x-ray beam and collimation of the detector. The reconstructed images clearly identified the locations of the two GNP-filled columns with different contrast levels directly proportional to gold concentration levels. On the other hand, the current pencil-beam implementation of XFCT is not yet practical for routine in vivo imaging tasks with GNPs, especially in terms of scanning time. Nevertheless, with the use of multiple detectors and a limited number of projections, it may still be used to image some objects smaller than the current phantom size. The current investigation suggests several modification strategies of the current XFCT setup, such as the adoption of the quasi-monochromatic cone/fan x-ray beam and XFCT-specific spatial filters or pinhole detector collimators, in order to establish the ultimate feasibility of a bench-top XFCT system for GNP-based preclinical molecular imaging applications.
This large analysis compared survival outcomes between postoperative CRT and RT alone in patients undergoing resection of high-risk major SGCs using a nationally representative database. The addition of concurrent chemotherapy to RT in patients with high-risk major SGCs did not offer an advantage in OS.
In this large database analysis of PORT for thymic tumors, PORT was associated with longer OS, with the greatest relative benefits observed for stage IIB to III disease and positive margins. In the absence of randomized studies assessing the value of PORT, these data may inform clinical practice.
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